| Novel Cinnamyl Hydroxyamides and 2-Aminoanilides as Histone Deacetylase Inhibitors: Apoptotic Induction and Cytodifferentiation Activity. | |
MedLine Citation:
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PMID: 21374822 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Four novel series of cinnamyl-containing histone deacetylase (HDAC) inhibitors 1-4 are described, containing hydroxamate (1 and 3) or 2-aminoanilide (2 and 4) derivatives. When screened against class I (maize HD1-B and human HDAC1) and class II (maize HD1-A and human HDAC4) HDACs, most hydroxamates and 2-aminoanilides displayed potent and selective inhibition toward class I enzymes. Immunoblotting analyses performed in U937 leukemia cells generally revealed high acetyl-H3 and low acetyl-α-tubulin levels. Exceptions are compounds 3 f-i, 3 m-o, and 4 k, which showed higher tubulin acetylation than SAHA. In U937 cells, cell-cycle blockade in either the G(2) /M or G(1) /S phase was observed with 1-4. Five hydroxamates (compounds 1 h-l) effected a two- to greater than threefold greater percent apoptosis than SAHA, and in the CD11c cytodifferentiation test some 2-aminoanilides belonging to both series 2 and 4 were more active than MS-275. The highest-scoring derivatives in terms of apoptosis (1 k, 1 l) or cytodifferentiation (2 c, 4 n) also showed antiproliferative activity in U937 cells, thus representing valuable tools for study in other cancer contexts. |
Authors:
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Sergio Valente; Maria Tardugno; Mariarosaria Conte; Roberto Cirilli; Andrea Perrone; Rino Ragno; Silvia Simeoni; Anna Tramontano; Silvio Massa; Angela Nebbioso; Marco Miceli; Gianluigi Franci; Gerald Brosch; Lucia Altucci; Antonello Mai |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-3-4 |
Journal Detail:
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Title: ChemMedChem Volume: - ISSN: 1860-7187 ISO Abbreviation: - Publication Date: 2011 Mar |
Date Detail:
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Created Date: 2011-3-4 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101259013 Medline TA: ChemMedChem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. |
Affiliation:
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Istituto Pasteur - Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Università degli Studi di Roma "La Sapienza", P.le A. Moro 5, 00185 Roma (Italy), Fax: (+39) 06-49693268. |
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